Solid-state synthesis, drug inclusion and 3D structure elucidation of a M12L8 cage-catenane

The solid-state synthesis and fast crystallization of poly-[ n ]-catenanes self-assembled of mechanically interlocked metal organic cages ( MOCs ) is virtually unexplored due to the lack of suitable crystals for single crystal X-ray diffraction (SC-XRD) analysis, limiting their progress as advanced functional materials. Here we report the unprecedented inclusion of paracetamol in the cavities of amorphous materials constituted of M 12 L 8 , interlocked MOCs synthesized by mechanochemistry (solid-state) under kinetic control . Full structure determination of a low-crystallinity and low-resolution powders of the M 12 L 8 poly-[ n ]-catenane including paracetamol has been carried out combining XRD data and Density Functional Theory (DFT) calculations using a multi-step approach. Each M 12 L 8 cage contains six paracetamol guests (of a maximum of 10 that can include) which is confirmed by thermal analysis and NMR spectroscopy. The drug loading has been also carried out by the instant synthesis method using a saturated paracetamol solution in which TPB and ZnI 2 self-assemble immediately (i.e., 1–5 seconds) encapsulating ⁓7 paracetamol molecules in the M 12 L 8 nanocages under kinetic control also giving a good selectivity. The cargo nature of the M 12 L 8 cages, the low toxicity of Zn(II) and the fact that 1 global in an aqueous media is disassembled releasing the drug, makes poly-[ n ]-catenane 1 global a potential drug delivery agent.